A P6(POL)-PROTEASE FUSION PROTEIN IS PRESENT IN MATURE PARTICLES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Human immunodeficiency virus type 1 (HIV-1) protease (PR) and p6(Pol) are translated as part of the Gag-Pol polyprotein after a ribosomal fr ameshift. PR is essential to virus replication and is responsible for cleaving Gag and Gag-Pol precursors, but the role of p6(Pol) in HIV-1 infection is poorly understood. Here, we report that (i) PR is present in mature HIV-1 virions primarily as a p6(Pol)-PR fusion protein; (ii ) HIV-1 PR cleaves viral precursor proteins expressed in bacterial cel ls at the Phe-Leu bond (positions 1639 to 1642) located at the junctio n of the NC and p6(Pol) proteins, releasing the p6(Pol)-PR fusion prot ein; and (iii) purified p6(Pol)-PR fusionprotein undergoes autocleavag e in vitro at at least three sites.